Bitter orange (Citrus aurantium) comes from a flowering evergreen tree of tropical Asia. Bitter orange trees are now widely grown in the Mediterranean region and elsewhere.

Bitter orange contains synephrine, a compound similar to ephedrine. The U.S. Food and Drug Administration (FDA) banned the sale of ephedrine-containing dietary supplements. Some products previously containing ephedrine have been reformulated to include bitter orange

Bitter orange is commonly used in dietary supplements for fat loss and as an appetite suppressant. It is claimed that bitter orange is an effective aid to weight loss and a safe alternative to ephedra. Various adverse effects have been contributed to bitter orange or p-synephrine. However, there is little concrete evidence to suggest the lack of safety of these products.

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

GRADE *

Use of bitter orange before surgery improved anxiety. A combination product with bitter orange improved symptoms associated with gallbladder removal. However, the effect of bitter orange alone is unclear. Further research is needed.

C

Limited research indicates that a combination product with bitter orange may improve symptoms of aging. However, more, high-quality studies are needed.

C

Bitter orange has been used in aromatherapy. Bitter orange does not seem to reduce combative, resistive behaviors in people with dementia. Further studies are needed on this topic.

C

Limited research reports that bitter orange may reduce blood sugar after meals and during fasting. Further studies on the effect of bitter orange alone are needed.

C

A combination of synephrine (a component of bitter orange) and caffeine may make exercise feel easier and increase blood pressure and blood sugar. Further research on bitter orange is needed.

C

Preliminary research shows promising results using bitter orange oil as an antifungal agent. However, further evidence is needed to confirm these results.

C

Early research suggests that bitter orange pills may benefit people with indigestion. Further research is needed before a conclusion may be made.

C

A component of bitter orange, p-synephrine, lacked effect on mood and energy. Further research is needed before a conclusion may be made.

C

Research suggests that weight loss may be enhanced by a bitter orange product. Additional high-quality studies on bitter orange alone are needed.

C

* Key to grades

A: Strong scientific evidence for this useB: Good scientific evidence for this useC: Unclear scientific evidence for this useD: Fair scientific evidence for this use (it may not work)F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

General: Up to 80 milligrams of p-synephrine (component of bitter orange) has been taken daily by mouth alone or in combination with other ingredients, including caffeine.

For an adjunct to surgery, one milliliter of bitter orange blossom per kilogram has been taken by mouth two hours before surgery.

For fungal infections, a 25% mixture of bitter orange oil three times daily, 20% bitter orange oil in alcohol three times daily, and 100% bitter orange oil once daily have been applied to the skin.

For indigestion, six grams of Zhizhu® pills containing bitter orange and other herbs has been taken by mouth three times daily after meals for four weeks.

For mood enhancement, V-8® juice containing 50 milligrams of p-synephrine from bitter orange extract (Advantra Z®) has been taken by mouth.

For weight loss, up to 80 milligrams of p-synephrine has been taken by mouth daily.

Children (younger than 18 years)

There is no proven safe or effective dose for bitter orange in children.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Avoid with known allergy or sensitivity to bitter orange, its constituents, or members of the Rutaceae family.

Side Effects and Warnings

Bitter orange is likely safe when taken by mouth in amounts normally found in food.

Bitter orange is possibly safe when the essential oil is used by inhalation as aromatherapy. Bitter orange is likely safe when taken by mouth at levels of up to 50 milligrams of p-synephrine or p-octopamine alone, or up to 40 milligrams p-synephrine or p-octopamine in combination with up to 320 milligrams of caffeine daily.

Bitter orange is likely safe when taken by mouth daily in single doses of up to 70 milligrams of p-synephrine alone or divided doses of up to 100 milligrams of p-synephrine alone. Bitter orange is likely safe when taken by mouth in single doses of 40 milligrams of p-synephrine in combination with 320 milligrams of caffeine or divided doses of 70 milligrams of p-synephrine in combination with 400 milligrams of caffeine.

Bitter orange may cause low blood pressure. Caution is advised in people taking drugs or herbs and supplements that lower blood pressure.

Bitter orange may lower blood sugar levels. Caution is advised in people with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

Use cautiously in people with gastrointestinal disorders, headache, heart disease, musculoskeletal disorders, narrow-angle glaucoma, respiratory disorders, or thyroid conditions. Use cautiously when bitter orange is taken alone or applied to the skin.

Avoid with known allergy or sensitivity to bitter orange, its constituents, or members of the Rutaceae family. Avoid bitter orange essential oil taken by mouth or applied to the skin. Avoid bitter orange in children or pregnant or breastfeeding women.

Note: Although various adverse and toxic effects have been attributed to bitter orange and/or p-synephrine, there is little concrete evidence to suggest the lack of safety of these products.

Pregnancy and Breastfeeding

There is a lack of sufficient data on the use of bitter orange during pregnancy or lactation. However, bitter orange is likely safe when taken in amounts commonly found as food.

It is suggested to avoid high doses of bitter orange, especially during lactation, due to its finding in combination with caffeine in weight loss products and the potential for decreased milk production.

Bitter orange may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

Bitter orange may interfere with the way the body processes certain drugs using the liver's cytochrome P450 enzyme system. As a result, the levels of these drugs may be increased in the blood and may cause increased effects or potentially serious adverse reactions. People using any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

Bitter orange may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

Bitter orange may interfere with the way the body processes certain herbs or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may become too high in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.

Bitter orange may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.